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Chronic exposure of nicotine modulates the expressions of the cerebellar glial glutamate transporters in Rats

Abstract

Rats were given nicotine (25 ppm) in their drinking water at the start of their mating period in order to study the expressions of glutamate transporter subtypes in cerebellar astrocytes following the chronic exposure of nicotine after mating. After the offspring were delivered, each group was divided into two subgroups. One group, the control group, was given distilled water only and the other group, the experimental group, was given distilled water containing nicotine. The cerebellar astrocytes were prepared from 7 day-old pups at each group. Ten days after the cells were cultured, the expression of the glutamate transporter subtypes (GLAST and GLT-1) was determined using immunochemistry and immunoblotting. During the continuous treatments, the developmental expression patterns of the GLAST and GLT-1 in the cerebellum were also determined from 2, 4 and 8 week-old rats. The expression levels of GLAST in cultured astrocytes of both the pre-or post-natally exposed groups were higher than those of the control group. However, these expression levels of the continuously exposed group were lower than those of the control group. Compared to those of the control group, the GLT-1 expression levels of all the nicotine-treated groups were higher, particularly in the continuously treated group.. According to the results from the immochemistry procedure, the cerebellar GLAST and GLT-1 expression levels of all nicotine-treated groups were lower than those of the control group at each age. However, the immunoblotting procedure showed that the cerebellar GLT-1 expression levels of all the nicotine-treated groups were higher than those of the control group, except for the rats that were continuously exposed for 8 weeks using immunoblotting. These results suggest that the expression of the glial GLAST and GLT-1 are altered differently depending on the initial exposure time and the partcicular period of nicotine exposure. In addition, nicotine exposure during gestation has persistent effects on glial cells.

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References

  • Ajarem, J. S. and Ahmad, M., Prenatal nicotine exposure modifies behavior of mice through early development.Pharmacol. Biochem. Behav., 59, 313–318 1993.

    Article  Google Scholar 

  • Akaike, A., Tamura, Y., Yokota, T., Shimohama, S., and Kimura J., Nicotine-induced protection of cultured cortical neurons againstN-methyl-D-aspartate receptor-mediated glutamate cytotoxicity.Brain Res., 644, 181–187 1994.

    PubMed  Article  CAS  Google Scholar 

  • Aramakis, V. B. and Metherate, R., Nicotine selectively enhances NMDA receptor-mediated synaptic transmission during postnatal development in sensory neocortex.J. Neurosci., 18, 8485–8495 (1998).

    PubMed  CAS  Google Scholar 

  • Arriza, J. L., Fairman, W. A., Wadiche, J. I., Murdoch, G. H., Kavanaugh, M. P., and Amara, S. G., Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex.J. Neurosci., 14, 5559–5569 1994.

    PubMed  CAS  Google Scholar 

  • Birtwistle, J. and Hall K., Does nicotine have beneficial effects in the treatment of certain diseases?Br. J. Nurs., 5, 1195–1202 (1997).

    Google Scholar 

  • Borlongan, C. V., Shytle, R. D., Ross, S. D., Shimizu, T., Freeman, T. B., Cahill, D. W., and Sanberg, P. R., (-)-Nicotine protects against systemic kainic acid-induced excitotoxic effects.Exp. Neurology, 136, 261–265 1995.

    Article  CAS  Google Scholar 

  • Bristol, L. A. and Rothstein, J. D., Glutamate transporter gene expression in amyotrophic lateral sclerosis motor cortex.Ann. Neurol., 39, 676–679 1996.

    PubMed  Article  CAS  Google Scholar 

  • Casado, M., Bendahan, A., Zafra, R., Danbolt, N. C., Aragon, C., Gimenez, C., and Kanner, B.I., Phosphorylation and modulation of brain glutamate transporters by protein kinase C.J. Biol. Chem., 268, 27313–27317 1993.

    PubMed  CAS  Google Scholar 

  • Collingridge, G. L. and Lester R. A. J., Excitatory amino acid receptors in the vertebrate central nervous system.Pharmacol. Rev., 41, 143–210 1989.

    PubMed  CAS  Google Scholar 

  • Conradt, M. and Stoffel, W., Inhibition of the high-affinity brain glutamate transporter GLAST via direct phosphorylation.J. Neurochem., 68, 1244–1251 1997.

    PubMed  CAS  Article  Google Scholar 

  • Fairman, W. A., Vandenverg, R. J., Arriza, J. L., Kavanaugh, M. P., and Amara, S. G., An excitatory amino acid transporter with properties of a ligand-gated chloride channel.Nature, 375, 599–603 1995.

    PubMed  Article  CAS  Google Scholar 

  • Fung, Y. K., Schmid, M. J., Anderson, T. M., and Lau Y., Effects of nicotine withdrawal on central dopaminergic systems.Pharmacol. Biochem. Behav., 53, 635–640 1996.

    PubMed  Article  CAS  Google Scholar 

  • Furuta, A., Rothstein, J. D., and Martin, L. J., Glutamate transporter protein subtypes are expressed differentially during rat CNS development.J. Neurosci., 17, 8363–8375 1997.

    PubMed  CAS  Google Scholar 

  • Garcia-Munoz, M., Patino, P., Young, S. J., and Groves P. M., Effects of nicotine on dopaminergic nigrostriatal axons requires stimulation of presynaptic glutamatergic receptors.J. Pharmacol. Exp. Ther., 277, 1685–1693 1996.

    PubMed  CAS  Google Scholar 

  • Gattu, M., Pauly, J. R., Boss, K. L., Summers, J. B., and Buccafusco J. J., Cognitive impairment in spontaneously hypertensive rats: role of central nicotinic receptors.Brain Res., 771, 89–103 1997.

    PubMed  Article  CAS  Google Scholar 

  • Gegelashvili, G. and Schousboe, A., High affinity glutamate transporters: Regulation of expression and activity.J. Pharmacol. Exp. Ther., 52, 6–15 1997.

    CAS  Google Scholar 

  • Hazell, A. S., Rao, K. V. R., Danbolt, N. C., Pow, D. V., and Butterworth, R. F., Selective down-regulation of the astrocyte glutamate transporters GLT-1 and GLAST within the medial thalamus in experimental Wernickes encepholopathy.J. Neurochem., 78, 560–568 2001.

    PubMed  Article  CAS  Google Scholar 

  • Kondo, K., Hashimoto, H., Kitanaka, J., Sawada, M., Suzumura, A., Marunouchi, T., and Baba, A., Expression of glutamate transporters in cultured glial cells.Neurosci. Lett., 188, 140–142 1995.

    PubMed  Article  CAS  Google Scholar 

  • Levy, L. M., Lehre, K. P., Walaas, S. I., Storm-Mathison, J., and Danbolt, N. C., Down-regulation of glial glutamate transporters after glutamatergic denervation in the rat brain.Eur. J. Neurosci., 7, 2036–2041 1995.

    PubMed  Article  CAS  Google Scholar 

  • Li, X., Zoli, M., Finnman, U., NeNovere, N., Changeux, J., and Fuxe, K., A single (-)-nicotine injection causes change with a time delay in the affinity of striatal D2 receptors for antagonist, but not for agonist, nor in the D2 receptor mRNA levels in the rat substantia nigra.Brain Res., 678, 157–167 1995.

    Article  Google Scholar 

  • Lim, D. K. and Kim H.S., Changes in the glutamate release and uptake of cerebellar cells in perinatally nicotine-exposed rat pups.Neurochem. Res., 26, 1119–1125 2001.

    PubMed  Article  CAS  Google Scholar 

  • Lim, D. K., Park, S. H., and Choi, W. J., Subacute nicotine exposure in cultured cerebellar cells increased the release and uptake of glutamate.Arch. Pharm. Res., 23, 488–494 2000.

    PubMed  CAS  Google Scholar 

  • LoPachin, R. M. and Aschner, M., Glial-neuronal interactions: Relevance to neurotoxic mechanisms.Toxicol. Appli. Pharmacol., 118, 141–158 1993.

    Article  CAS  Google Scholar 

  • Lowry, O. H., Rosebrough, N. J., Fair, A. L., and Randall, R. J., Protein measurement with the Folin phenol reagent.J. Biol. Chem., 193, 265–275 1951.

    PubMed  CAS  Google Scholar 

  • Martin, B. R., Nicotine receptors in the central nervous system. In Conn, P. M. (Ed),The receptors. Academic Press, New York, pp. 393–415 (1986).

    Google Scholar 

  • McCaslin, P. P. and Morgan, W. W., Cultured cerebellar cells as in vitro model of excitatory amino acid receptor function.Brain Res., 417, 380–384 1987.

    PubMed  Article  CAS  Google Scholar 

  • Meldrum, B. and Garthwaite, J., Excitatory amino acid neurotoxicity and neurodegenerative disease.Trends Pharmacol. Sci., 11, 379–387 1990.

    PubMed  Article  CAS  Google Scholar 

  • Mennerick, S. and Zorumski, C. F., Glial contribution to excitatory neurotransmission in cultured hippocampal cells.Nature, 368, 59–62 1994.

    PubMed  Article  CAS  Google Scholar 

  • Nakayama, H., Numakawa, T., Ikeuchi, T., and Hatanaka, H., Nicotine-induced phosphorylation of extracellual signalregulated protein kinase and CREB in PC12h cells.J. Neurochem., 79, 489–498 2001.

    PubMed  Article  CAS  Google Scholar 

  • Newman, M. B., Shytle, R. D., and Sanberg, P. R., Locomotor behavioral effects of prenatal and postnatal nicotine exposure in rat offspring.Behav. Pharmacol., 10, 700–706 1999.

    Google Scholar 

  • Nicholis, D. and Attwell, D., The release and uptake of excitatory amino acids.Trends Pharmacol. Sci., 11, 462–468 1990.

    Article  Google Scholar 

  • Nordberg, A., Zhang, X., Fredriksson, A., and Eriksson, P., Neonatal nicotine exposure induces permanent changes in brain nicotine receptors and behaviour in adult mice.Dev. Brain Res., 63, 201–207 1991.

    Article  CAS  Google Scholar 

  • Perez De La Mora, M., Mendez-Franco, J., Salceda, R., Aguirre, J. A., and Fuxe, K., Neurochemical effects of nicotine on glutamate and GABA mechanisms in the rat brain.Acta. Physiol. Scand., 141, 241–250 1991.

    PubMed  CAS  Article  Google Scholar 

  • Rao, V. L. R., Rao, A. M., Dogan, A., Bowen, K. K., Hatcher, J., Rothstein, J. D., and Demsey, R. J., Glial glutamate transporter GLT-1 down-regulation precedes delayed neuronal death in gerbril hippocampus following transient global cerebral ischemia.Neuchem. Int., 36, 531–537 2000.

    CAS  Google Scholar 

  • Rop, P. P., Grimaldi, R., Oddoze, C., and Viala, A., Determination of nicotine and its main metabolites in urine by high performance liquid chromatography.J. Chromatogr., 612, 302–309 1993.

    PubMed  Article  CAS  Google Scholar 

  • Roth, R. H., Elsworth, J. D., and Morrow, B. A., Prenatal nicotine exposure disrupts short-term memory in spontaneous object recognition task.Soc. Neurosci. Abs., 26, Parti, 1095 (2000).

    Google Scholar 

  • Rothstein, J. D., Dykes-Hoberg, M., Pardo, C. A., Bristol, L. A., Jin, L., Kuncl, R. W., Kanai, Y., Hediger, M., Wang, Y., Schieke, J. P., and Welty, D. F., Knockout of glutamate transporters reveals a major role for astroglia transport in excitotoxicity and clearance of glutamate.Neuron, 16, 675–686 1996.

    PubMed  Article  CAS  Google Scholar 

  • Seal, R. P. and Amara, S. G., Excitatory amino acid transporters: A family in flux.Annu. Rev. Pharmacol. Toxicol., 39, 431–456 1999.

    PubMed  Article  CAS  Google Scholar 

  • Sutherland, M. L., Delaney, T. A., and Noebel, J. L., Glutamate transporter mRNA expression in proliferative zones of the developing and adult murine CNS.J. Neurosci., 16, 2191–2207 1996.

    PubMed  CAS  Google Scholar 

  • Swanson, R. A., Liu, J., Miller, J. M., Rothstein, J. D., Rarrell, K., Stein, B. A., and Longuemare, M. C., Neuronal regulation of glutamate transporter subtype expression in astrocytes.J. Neurosci., 17, 932–940 1997.

    PubMed  CAS  Google Scholar 

  • Tang, G., Hanna, S. T., and wang, R., Effects of nicotine on K+ channel currents in vascular smooth muscle cells rat tail arteries.Eur. J. Pharmacol., 364, 247–254 1999.

    PubMed  Article  CAS  Google Scholar 

  • Thomas, J. D., Garrison, M. E., Slawecki, C. J., Ehlers, C. L., and Riley, E. P., Nicotine exposure during the neonatal brain growth spurt produces hyperactivity in preweanling rats.Neurotoxicol. Teratol., 22, 695–701 2000.

    PubMed  Article  CAS  Google Scholar 

  • Tizabi, Y., Russell, L. T., Nespor, S. M., Perry, D. C., and Grunberg, N. E., Prenatal nicotine exposure: Effects on locomotor activity and central [125l]α-BT binding in rats.Pharmacol. Biochem. Behav., 66, 495–500 2000.

    PubMed  Article  CAS  Google Scholar 

  • Trotti, D., Rizzini, B. L., Rossi, D., Haugeto, O., Racagni, G., Danbolt, N. C., and Volterra, A., Neuronal and glial glutamate transporters possess an SH-based redox regulatory mechanism.Eur. J. Neurosci., 9, 1236–1243 1997.

    PubMed  Article  CAS  Google Scholar 

  • Tzavara, E. T., Monory, K., Hanoune, J., and Nomikos, G. G., Nicotine withdrawal syndrome: behabioural distress and selective up-regulation of the cyclic AMP pathway in the amygdala.Eur. J. Neurosci., 16, 149–153 2002.

    PubMed  Article  Google Scholar 

  • Zhang, X., Gong, Z., and Nordberg, A., Effects of chronic treatment with (+)- and (-)-nicotine on nicotinic acetylcholine receptors andN-methyl-D-aspartate receptors in rat brain.Brain Res., 644, 32–39 1994.

    PubMed  Article  CAS  Google Scholar 

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Correspondence to Dong Koo Lim.

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Lim, D.K., Kim, H.S. Chronic exposure of nicotine modulates the expressions of the cerebellar glial glutamate transporters in Rats. Arch Pharm Res 26, 321–329 (2003). https://doi.org/10.1007/BF02976963

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Key words

  • Nicotine
  • Cerebellum
  • GLAST
  • GLT-1